Back-calculating Your IND timeline

Welcome back to Tox & Trials, a newsletter that gives you a first-hand, raw, educational view of toxicology in the pharmaceutical industry.

This week on Tox & Trials, we are breaking down the timeline to IND - backwards.

Many times when people think of the road to an IND, they think of it in chronological order. I need to discover a molecule, then I need to optimize it, then I need to make sure it works in animals, then I need to find the tox thresholds, then I can author the IND, then I can submit the IND.

This is all good and well when you’re trying to understand where you need to go, but when planning the timelines in conjunction with all the other things that need to happen (eg, budgeting, business objectives, test article generation, etc.) it is easier to work backwards from the IND submission.

So, where do we start?

The first step is figuring out when you want your IND to be submitted. This is typically heavily driven by the top dogs, but for our purposes, today we can pretend we get to choose.

So, let’s say we have a company called OncoBio and our first drug is in development, ONC123. We want ONC123 to be submitted under an IND in December of 2028. Now, we work backwards:

December 2028 - ONC123 IND Submission

The time to author an IND is roughly 3-6 months. Let’s use 4 for easy numbers. This means that IND authoring needs to initiate in September 2028:

December 2028 - ONC123 IND Submission

September 2028 - ONC123 IND Authoring Initiation

In order to initiate authoring of the IND, our GLP tox studies need to be completed OR at least have an audited draft (AD) report. If we are working with a standard small molecule oral drug, then we will likely be running a standard 28-day GLP tox study in the rat and dog. From protocol development to Final Report is roughly 6 months for these studies which means that we would need to initiate protocol development of our GLP tox by March 2028:

December 2028 - ONC123 IND Submission

September 2028 - ONC123 IND Authoring Initiation

March 2028 - ONC123 GLP Rat and GLP Dog Initiation

Now, in order for the GLP tox studies to get the go ahead, we will need test article to support them. And not just any TA - clinical grade TA. The range for generating TA can widely vary, but for today we will use 6 months. So if we want to initiate our GLP tox in March 2028 then we need TA ready by March 2028 which means we need to start the process of manufacturing the TA by October 2027:

December 2028 - ONC123 IND Submission

September 2028 - ONC123 IND Authoring Initiation

March 2028 - ONC123 GLP Rat and GLP Dog Initiation

October 2027 - ONC123 Clinical TA Manufacturing Initiation

While the TA is being generated, other studies will be run during that time - for example, any PK studies, assays, last minute efficacy studies, etc. But by using the TA manufacturing as the trigger for decision making on the GLP tox, we can continue to work backwards. To support that trigger, we need our DC-enabling studies - or our nonGLP DRF tox studies - to be pretty well along. They don’t necessarily have to be complete, but most boards will want at least the histopath data in hand before making that final go/no-go decision on your multi-million dollar GLP tox studies. Your DC-enabling studies will usually take around 3 months, putting initiation of these studies in the July 2027 timeframe:

December 2028 - ONC123 IND Submission

September 2028 - ONC123 IND Authoring Initiation

March 2028 - ONC123 GLP Rat and GLP Dog Initiation

October 2027 - ONC123 Clinical TA Manufacturing Initiation

July 2027 - ONC123 DC-enabling Study Initiation

But, in order for your DC-enabling studies to happen we need to have made the decision to move one molecule along in development which means we will have needed to run our efficacy studies and our PK studies to be confident enough that our drug will not only work but measure up to clinical and marketing requirements. This phase can also very widely, because there will be a lot of back and forth between the preclinical groups of chemistry, research, biology, tox, etc. all trying to find and justify the best molecule to go to DC. For today, let’s say this process takes about 1 year, putting your Preclinical phase at July 2026:

December 2028 - ONC123 IND Submission

September 2028 - ONC123 IND Authoring Initiation

March 2028 - ONC123 GLP Rat and GLP Dog Initiation

October 2027 - ONC123 Clinical TA Manufacturing Initiation

July 2027 - ONC123 DC-enabling Study Initiation

July 2026 - ONC123 Preclinical Phase

And if we put it all together:

So, if you want to start a startup and you’re trying to figure out when the soonest you could potentially file an IND and get into the clinic, this is a good starting point. This is also very skeleton worthy, meaning there’s a lot of other variables that go into this process not listed here.

Overall, it gives you a good idea of the things we need to think about to go from 0 to 1 - and how heavily weighted the tox studies are in that thinking.

Until next time!

Dessi McEntee is a board-certified toxicologist with extensive experience in bringing new medicines to the clinic and beyond through well-executed nonclinical development programs and strategy. She delivers Tox & Trials in an effort to help educate on the nuances of navigating nonclinical safety and toxicology within drug development, a commonly misunderstood or under-understood piece of the pharmaceutical pipeline.

For more information on Dessi, visit www.toxistrategy.com.